Project Detail
Interagency Autism Coordinating Committee (IACC) logo
Office of Autism Research Coordination (OARC) logo

Genomic hotspots of autism  

Studies focusing on specific genes have made limited progress in unraveling the complex genetics of autism spectrum disorders. Evan Eichler and his colleagues at the University of Washington plan a broad and systematic approach to uncover autism-linked genes by scouring the fragile regions of DNA for sporadic, non-inherited deletions or duplications. Eichler and his colleagues have found that specific regions of the genome are more prone to spontaneous and inherited genetic alterations than other regions. These genomic 'hotspots' are at risk of copy-number variants (deletions or duplications) because they are susceptible to breakage. Hotspots are associated with a wide range of diseases, including autism, intellectual disability, congenital birth defects and epilepsy. Eichler and his team propose to search through approximately 1,000 hotspots for autism-associated genes by looking for deletions and duplications, which they predict will be more frequent and thus easier to find than inherited mutations that correlate with the disorder. The researchers first mined data from the Simons Simplex Collection (SSC), a repository of blood samples from families that have one child with autism, but unaffected parents and siblings. To date, the researchers have analyzed genomic hotspots from 1,500 SSC families and identified 96 copy-number variants unique to families with autism. These include both sporadic and inherited mutations that disrupt important neurologically relevant genes, making them candidates for an association with autism. Eichler's team is complementing these studies with complete sequencing of all genes in 200 SSC families. The initial results support a 'two-hit' model of autism, in which recurrent mutations in genomic hotspots along with disruptive smaller point mutations in other genes may together explain variability in autism genetics. The researchers also plan to collect and analyze samples from an additional 1,000 families with more broadly defined autism spectrum disorders and developmental delay. They hope to learn whether specific features of the disorders, such as developmental defects and behavioral problems, are associated with particular mutations or chromosomal defects. Project Status


Funder Simons Foundation
Fiscal Year Funding $588,027.00
Current Award Period 2009-2012
Project Number 137578
Principal Investigator Eichler, Evan
Received ARRA Funding? No
Strategic Plan Question Question 3: What Caused This To Happen And Can This Be Prevented? (Causes)
Subcategory Genetic Risk Factors
Strategic Plan Objective Green dot: Objective has greater than or equal to the recommended funding. 3LB. Identify genetic risk factors in at least 50% of people with ASD by 2014. IACC Recommended Budget: $33,900,000 over 6 years.
Federal or Private? Private
Institution University of Washington
State/Country Washington
Web Link 1 Genomic hotspots of autism (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
New! History/Related Projects Genomic hotspots of autism | $232,692.00 | 2009 | 137578